BACKGROUND & AIMS: BACKGROUND:Left atrial enlargement, a sensitive integrator of left ventricular diastolic function, is associated with increased cardiovascular morbidity and mortality. Vitamin D is linked to lower cardiovascular morbidity, possibly modifying cardiac structure and function; however, firm evidence is lacking. We assessed the effect of an activated vitamin D analog on left atrial volume index (LAVi) in a post hoc analysis of the PRIMO trial (clinicaltrials.gov: NCT00497146). METHODS AND RESULTS:One hundred ninety-six patients with chronic kidney disease (estimated glomerular filtration rate 15-60 mL/min per 1.73 m(2)), mild to moderate left ventricular hypertrophy, and preserved ejection fraction were randomly assigned to 2 μg of oral paricalcitol or matching placebo for 48 weeks. Two-dimensional echocardiography was obtained at baseline and at 24 and 48 weeks after initiation of therapy. Over the study period, there was a significant decrease in LAVi (-2.79 mL/m(2), 95% CI -4.00 to -1.59 mL/m(2)) in the paricalcitol group compared with the placebo group (-0.70 mL/m(2) [95% CI -1.93 to 0.53 mL/m(2)], P = .002). Paricalcitol also attenuated the rise in levels of brain natriuretic peptide (10.8% in paricalcitol vs 21.3% in placebo, P = .02). For the entire population, the change in brain natriuretic peptide correlated with change in LAVi (r = 0.17, P = .03). CONCLUSIONS:Forty-eight weeks of therapy with an active vitamin D analog reduces LAVi and attenuates the rise of BNP. In a population where only few therapies alter cardiovascular related morbidity and mortality, these post hoc results warrant further confirmation.

背景与目标：

BACKGROUND & AIMS: :Vitamin D and its analogues exhibit potent antitumor effects in many tissues, including the pancreas. Normal and malignant pancreatic tissues were recently shown to express high levels of vitamin D 1-alpha-hydroxylase, which converts circulating 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D. We examined associations between dietary intake of vitamin D, calcium, and retinol and subsequent risk for pancreatic cancer. We conducted prospective studies in cohorts of 46,771 men ages 40 to 75 years as of 1986 (the Health Professionals Follow-up Study), and 75,427 women ages 38 to 65 years as of 1984 (the Nurses' Health Study), documenting incident pancreatic cancer through the year 2000. Diet was ascertained by semiquantitative food-frequency questionnaire. We identified 365 incident cases of pancreatic cancer over 16 years of follow-up. Compared with participants in the lowest category of total vitamin D intake (<150 IU/d), pooled multivariate relative risks for pancreatic cancer were 0.78 [95% confidence interval (95% CI), 0.59-1.01] for 150 to 299 IU/d, 0.57 (95% CI, 0.40-0.83) for 300 to 449 IU/d, 0.56 (95% CI, 0.36-0.87) for 450 to 599 IU/d, and 0.59 (95% CI, 0.40-0.88) for >/=600 IU/d (P(trend) = 0.01). These associations may be stronger in men than women. After adjusting for vitamin D intake, calcium and retinol intakes were not associated with pancreatic cancer risk. In two U.S. cohorts, higher intakes of vitamin D were associated with lower risks for pancreatic cancer. Our results point to a potential role for vitamin D in the pathogenesis and prevention of pancreatic cancer.

背景与目标： : 维生素d及其类似物在包括胰腺在内的许多组织中表现出有效的抗肿瘤作用。最近显示正常和恶性胰腺组织表达高水平的维生素d 1-α-羟化酶，可将循环中的25-羟基维生素d转化为活性的1,25-二羟基维生素d。我们研究了饮食中维生素d，钙和视黄醇的摄入量与胰腺癌后续风险之间的关联。我们对46,771名年龄在40 ~ 75岁的男性作为1986年 (健康专业人员随访研究) 和75,427名年龄在38 ~ 65岁的女性作为1984年 (护士健康研究) 进行了前瞻性研究，记录了通过2000年发生的胰腺癌。通过半定量食物频率问卷确定饮食。在16年的随访中，我们确定了365例胰腺癌事件。与维生素d总摄入量最低类别 (<150 IU/D) 的参与者相比，胰腺癌的合并多变量相对风险被0.78 [95% 置信区间 (95% CI)，0.59-1.01] 150至299 IU/d，0.57 (95% CI，0.40-0.83) 300至449 IU/d，0.56 (95% CI，0.36-0.87) 450至599 IU/d，0.59 (95% CI，0.40-0.88)>/= 600 IU/d (P (趋势) = 0.01)。这些联想在男性中可能比女性更强。调整维生素d摄入量后，钙和视黄醇的摄入量与胰腺癌风险无关。在两个美国队列中，较高的维生素d摄入量与较低的胰腺癌风险相关。我们的结果指出维生素d在胰腺癌的发病机理和预防中的潜在作用。

BACKGROUND & AIMS: BACKGROUND:Type 1 diabetes (T1D) is an autoimmune disease which is characterised by the destruction of insulin-producing beta cells in human pancreas leading consequently to a hyperglycaemic metabolism. Recent studies have shown that low cholecalciferol (25(OH)D3) concentrations may contribute to the development of T1D. The 25(OH)D3 status depends mostly on human skin production influenced by exposure to UVB radiation. Our intention was to examine whether there was a change in UVB radiation in the past years and if this has an impact on patients' vitamin D status. METHODS:We analysed the 25(OH)D3 concentration of blood samples from 287 T1D patients in the years 2004-2007 at the University Hospital Frankfurt. Moreover, daily UVB irradiation data of this time were received. Wilcoxon-Mann-Whitney test and Spearman correlation test were used for statistical analyses. RESULTS:We observe a strong correlation between UVB irradiation and the 25(OH)D3 concentration of German T1D patients (correlation coefficient=rho=0.56, p=7×10(-3)). Moreover, 25(OH)D3 blood levels obtained in summer (Apr-Oct) were significantly higher than in the winter season (p=8×10(-3)). In the years 2004-2007 there was a significant decline of UVB radiation in the summers (rho=-0.21, p<10(-6)) but no change was found in (rho=-0.07, p=0.12). This corresponds to a significant decrease of 25(OH)D3 levels in T1D patients over the summers (rho=-0.24, p=2×10(-3)) but not in winters (rho=-0.03, p=0.73). CONCLUSION:Our results reveal a significant correlation of UVB irradiation and the vitamin D concentration of German T1D patients. A decrease of UVB irradiation over the summers 2004-2007 is accompanied by a decline of 25(OH)D3 levels observed in those summer months which may indicate a local time trend requiring further investigation into the environmental factors of vitamin D deficiency. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

背景与目标：

BACKGROUND & AIMS: :Vitamin D deficiency is associated with osteoporosis and is thought to increase the risk of cancer and CVD. Despite these numerous potential health effects, data on vitamin D status at the population level and within key subgroups are limited. The aims of the present study were to examine patterns of 25-hydroxyvitamin D (25(OH)D) levels worldwide and to assess differences by age, sex and region. In a systematic literature review using the Medline and EMBASE databases, we identified 195 studies conducted in forty-four countries involving more than 168 000 participants. Mean population-level 25(OH)D values varied considerably across the studies (range 4·9-136·2 nmol/l), with 37·3 % of the studies reporting mean values below 50 nmol/l. The highest 25(OH)D values were observed in North America. Although age-related differences were observed in the Asia/Pacific and Middle East/Africa regions, they were not observed elsewhere and sex-related differences were not observed in any region. Substantial heterogeneity between the studies precluded drawing conclusions on overall vitamin D status at the population level. Exploratory analyses, however, suggested that newborns and institutionalised elderly from several regions worldwide appeared to be at a generally higher risk of exhibiting lower 25(OH)D values. Substantial details on worldwide patterns of vitamin D status at the population level and within key subgroups are needed to inform public health policy development to reduce risk for potential health consequences of an inadequate vitamin D status.

背景与目标： 维生素d缺乏与骨质疏松症有关，被认为会增加患癌症和CVD的风险。尽管有这些潜在的健康影响，但人口水平和关键亚组中维生素d状况的数据有限。本研究的目的是检查世界范围内25-羟基维生素d (25(OH)D) 水平的模式，并评估年龄，性别和地区的差异。在使用Medline和EMBASE数据库的系统文献综述中，我们确定了在44个国家进行的195项研究，涉及168 000多名参与者。在整个研究中，平均人口水平25(OH) d值差异很大 (范围为4·9-136·2 nmol/l)，37·3% 的研究报告平均值低于50 nmol/l。在北美观察到最高的25(OH) d值。尽管在亚洲/太平洋和中东/非洲地区观察到与年龄相关的差异，在其他地方没有观察到它们，在任何地区也没有观察到性别相关的差异。研究之间的实质性异质性排除了对人口水平总体维生素d状况的结论。然而，探索性分析，建议来自世界各地的几个地区的新生儿和住院老人似乎普遍处于较低的25(OH) d值的较高风险中。需要在人口水平和关键亚组中详细了解全球范围内的维生素d状况，以告知公共卫生政策制定以降低潜在健康后果的风险维生素d水平不足。

BACKGROUND & AIMS: :Vitamin K was discovered fortuitously in 1929 as part of experiments on sterol metabolism and was immediately associated with blood coagulation. In the decade that followed, the principal K vitamers, phylloquinone and the menaquinones, were isolated and fully characterized. In the early 1940s, the first vitamin K antagonists were discovered and crystallized with one of its derivatives, warfarin, still being widely used in today's clinical setting. However, major progress in our understanding of the mechanisms of action of vitamin K came in the 1970s with the discovery of γ-carboxyglutamic acid (Gla), a new amino acid common to all vitamin K proteins. This discovery not only provided the basis to understanding earlier findings about prothrombin but later led to the discovery of vitamin K-dependent proteins (VKDPs) not involved in hemostasis. The 1970s also saw an important breakthrough with respect to our understanding of the vitamin K cycle and marked the discovery of the first bone VKDP, osteocalcin. Important studies relating to the role of vitamin K in sphingolipid synthesis were also underway at that time and would pave the way to further work 15 years later. The decades that followed saw the discovery of additional VKDPs showing wide tissue distribution and functional scope, the latest members having been identified in 2008. The 1990s and 2000s were also marked by important epidemiological and intervention studies that focused on the translational impact of recent vitamin K discoveries, notably with respect to bone and cardiovascular health. This short review presents an overview of the history of vitamin K and of its recent developments.

背景与目标： : 维生素k在甾醇代谢实验中被发现1929年，并立即与血液凝固有关。在随后的十年中，分离并充分表征了主要的K维生素，叶绿醌和menaquinones。在20世纪40年代初中，发现了第一批维生素k拮抗剂，并以其衍生物之一华法林结晶，在当今的临床环境中仍被广泛使用。然而，20世纪70年代发现了 γ-羧基谷氨酸 (Gla)，这是所有维生素k蛋白共有的新氨基酸，因此我们对维生素k作用机制的理解取得了重大进展。这一发现不仅为理解早期关于凝血酶原的发现提供了基础，而且后来导致发现了不参与止血的维生素k依赖性蛋白 (VKDPs)。该20世纪70年代在我们对维生素k循环的理解方面也取得了重要突破，并标志着第一个骨VKDP (骨钙素) 的发现。有关维生素k在鞘脂合成中的作用的重要研究也在当时进行，并将为15年后的进一步工作铺平道路。在随后的几十年中，发现了其他vkdp，显示出广泛的组织分布和功能范围，2008年发现了最新的成员。20世纪90年代和21世纪00年代还以重要的流行病学和干预研究为标志，这些研究侧重于最近发现的维生素k的转化影响，尤其是在骨骼和心血管健康方面。这篇简短的评论概述了维生素k的历史及其最新发展。

BACKGROUND & AIMS: :The purpose of this study was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. The present study examined protein and vitamins, and their interactions. This study was based on three-way ANOVA; the three factors were lighting conditions, dietary protein and dietary vitamins, respectively. The levels of dietary protein were low or normal: 9% casein or 20% casein. The levels of dietary vitamins were low, normal or high: 1/3.3 of normal (AIN-93G diet) content, normal content, or three times the normal content, respectively. Other compositions were the same as those of the AIN-93G diet, and six kinds of experimental diet were prepared. Four-week-old rats (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h light/dark cycle) for 4 wk. After 4 wk, the gonadal weights and serum testosterone content were evaluated. In the constant darkness groups (D-groups), the low-protein diet induced reduction of gonadal organ weights and serum testosterone concentrations. This reduction of gonadal organ weights was exacerbated by progressively higher levels of dietary vitamins. In the case of a normal-protein diet, the depression of gonadal development was not accelerated by high-vitamin intake. In the normal lighting groups (N-groups), the low-protein and high-vitamin diet slightly depressed gonadal development. These results suggest that the metabolism of protein and vitamins is different in rats being kept under constant darkness, and that excess dietary vitamins have an adverse effect on gonadal development in rats fed a low-protein diet.

背景与目标： : 这项研究的目的是阐明营养物质对持续处于黑暗状态下的雄性大鼠性腺发育的影响，以此作为每日节律紊乱的模型。本研究检查了蛋白质和维生素及其相互作用。本研究基于三次方差分析; 这三个因素分别是光照条件、膳食蛋白质和膳食维生素。膳食蛋白质水平低或正常: 9% 酪蛋白或20% 酪蛋白。饮食中的维生素水平低，正常或高: 正常 (AIN-93G饮食) 含量的1/3.3，正常含量或正常含量的3倍。其他组成与AIN-93G饮食相同，并准备了六种实验饮食。将4周龄的大鼠 (Fischer 344品系) 保持在恒定的黑暗或正常照明下 (12小时的光/暗周期) 4周。4周后，评估性腺重量和血清睾丸激素含量。在恒定的黑暗组 (D组) 中，低蛋白饮食导致性腺器官重量和血清睾丸激素浓度降低。饮食中维生素的含量逐渐增加，加剧了性腺器官重量的减少。在正常蛋白质饮食的情况下，高维生素摄入量不会加速性腺发育的抑制。在正常照明组 (N组) 中，低蛋白和高维生素饮食会稍微抑制性腺发育。这些结果表明，在持续黑暗的情况下，大鼠的蛋白质和维生素的代谢是不同的，并且过量的饮食维生素对喂养低蛋白饮食的大鼠的性腺发育有不利影响。

BACKGROUND & AIMS: OBJECTIVE:To review recent evidence that suggests vitamin B12 is associated with risk reduction for some chronic diseases and birth defects. QUALITY OF EVIDENCE:A MEDLINE search from 1999 to 2007 was performed using the key word vitamin B12. The most relevant articles (129) dealt with cardiovascular disease, cancer, mental health, and birth outcomes;most studies presented level II evidence. MAIN MESSAGE:Vitamin B12 might confer health benefits; however, such benefits are difficult to ascertain because of the complementary functions of vitamin B12 and folic acid. Vitamin B12 might lower high homocysteine levels below a threshold level achieved by folic acid alone. Furthermore, the interactions between the nutritional environment and genotype might have an important influence on vitamin B12, chronic disease risk, and risk of neural tube defects. CONCLUSION:Vitamin B12 might help protect against chronic disease and neural tube defects, but more research, particularly in the area of nutritional genomics, is needed to determine how vitamin B12 might augment the benefits of folic acid. Some consideration should be given to the potential value of fortifying foods with vitamin B12 in addition to the current mandatory folic acid fortification of grains.

背景与目标：

BACKGROUND & AIMS: :The purpose of this review is to summarize the peer-reviewed literature in relation to sunlight exposure assessment and the validity of using sunlight exposure questionnaires to quantify vitamin D status. There is greater variability in personal ultraviolet (UV) light exposure as the result of personal behavior than as the result of ambient UV light exposure. Although statistically significant, the correlation coefficients for the relation between personal report of sun exposure and ambient UV light measured by dosimetry (assessment of radiation dose) are relatively low. Moreover, the few studies to assess the relation between sunlight measures and serum 25-hydroxyvitamin D show low correlations. These low correlations may not be surprising given that personal factors like melanin content in skin and age also influence cutaneous synthesis of vitamin D. In summary, sunlight exposure questionnaires currently provide imprecise estimates of vitamin D status. Research should be directed to develop more objective, nonintrusive, and economical measures of sunlight exposure to quantify personal vitamin D status.

背景与目标： : 本综述的目的是总结与阳光暴露评估有关的同行评审文献，以及使用阳光暴露问卷量化维生素d状态的有效性。由于个人行为的结果，个人紫外线 (UV) 光暴露比环境紫外线暴露的结果具有更大的可变性。尽管具有统计学意义，但通过剂量测定法 (辐射剂量评估) 测量的个人日晒报告与环境紫外线之间关系的相关系数相对较低。此外，评估阳光测量与血清25-羟基维生素d之间关系的研究很少，但相关性较低。鉴于皮肤和年龄中的黑色素含量等个人因素也会影响皮肤维生素d的合成，因此这些低相关性可能不足为奇。总之，阳光暴露问卷目前提供了不精确的维生素d状况估计。应该进行研究，以开发更客观，非侵入性和经济的日光照射措施，以量化个人维生素d的状况。

BACKGROUND & AIMS: BACKGROUND:Atherosclerotic cardiovascular disease is the most common cause of death among hemodialysis patients; it has been attributed to increased oxidative stress, dyslipidemia, malnutrition, and chronic inflammation. Activation of neutrophils is a well-recognized feature in dialysis patients, and superoxide-anion production by neutrophil NADPH oxidase may contribute significantly to oxidative stress. OBJECTIVE:The aim of the study was to compare the effects of dietary supplementation with concentrated red grape juice (RGJ), a source of polyphenols, and vitamin E on neutrophil NADPH oxidase activity and other cardiovascular risk factors in hemodialysis patients. DESIGN:Thirty-two patients undergoing hemodialysis were recruited and randomly assigned to groups to receive dietary supplementation with RGJ, vitamin E, or both or a control condition without supplementation or placebo. Blood was obtained at baseline and on days 7 and 14 of treatment. RESULTS:RGJ consumption but not vitamin E consumption reduced plasma concentrations of total cholesterol and apolipoprotein B and increased those of HDL cholesterol. Both RGJ and vitamin E reduced plasma concentrations of oxidized LDL and ex vivo neutrophil NADPH oxidase activity. These effects were intensified when the supplements were used in combination; in that case, reductions in the inflammatory biomarkers intercellular adhesion molecule 1 and monocyte chemoattractant protein 1 also were observed. CONCLUSIONS:Regular ingestion of concentrated RGJ by hemodialysis patients reduces neutrophil NADPH-oxidase activity and plasma concentrations of oxidized LDL and inflammatory biomarkers to a greater extent than does that of vitamin E. This effect of RGJ consumption may favor a reduction in cardiovascular risk.

背景与目标：

BACKGROUND & AIMS: :Biotin deficiency (Bt-D) is usually studied at the point at which the animal model exhibits the signs of full-blown deficiency symptoms; in rats, this typically occurs at 6-8 weeks of feeding a deficient diet. To differentiate specific deficiency effects from those of undernutrition, biotin sufficient and deficient rats were studied at 2, 3, 4, and 5 weeks on the deficiency diet, before the onset of weight loss and deficiency signs. The deficiency state was confirmed by biochemical and molecular analyses. Blood and liver metabolites were determined and western blots of signaling proteins, and qRT-PCR gene expression studies. The main effects of Bt-D were already well established by the fourth week on the diet; thus, we consider the fourth week as the optimum time to study the consequences of biotin depletion. Early effects, which were already apparent at week 2, included cellular energy deficit (as assessed by increased AMP/ATP ratio), activation of the AMPK energy sensor, and changes of carbon metabolism gene transcripts (e.g., phosphoenolpyruvate carboxykinase, carnitine palmitoyl transferase 1, liver glucokinase and fatty acid synthetase). Reduced post-prandial blood concentrations of glucose were also observed early; we speculate that these are attributable to augmented sensitivity to insulin and increased glucose utilization, a likely effect of AMPK induction of translocation of glucose transporter GLUT4 to the cell membranes and increased hexokinase expression. Other late-onset changes (week 4) included increased serum concentrations of lactate and free fatty acids and decreased liver glycogen and serum concentrations of triglycerides and total cholesterol. The identification of the early specific molecular and metabolic disturbances of biotin deficiency might be useful in identifying individuals with marginal deficiency of this vitamin, which appears to be common in normal human pregnancy. The study of time-course of other vitamin deficiencies, such as this one, might help to better understand and cope with their effects.

背景与目标： : 生物素缺乏症 (bt-d) 通常在动物模型表现出完全缺乏症状的迹象时进行研究; 在大鼠中，这通常发生在喂养缺乏饮食的6-8周时。为了区分特定的缺乏症影响与营养不良的影响，在体重减轻和缺乏症状开始之前，在缺乏饮食的第2、3、4和5周研究了生物素充足和缺乏的大鼠。通过生化和分子分析证实了缺陷状态。测定了血液和肝脏代谢产物，并对信号蛋白进行了western印迹，并进行了qRT-PCR基因表达研究。到第四周，bt-d的主要作用已经在饮食上得到很好的确立; 因此，我们认为第四周是研究生物素耗竭后果的最佳时间。早期影响 (在第2周已经很明显) 包括细胞能量不足 (通过增加AMP/ATP比率评估)，AMPK能量传感器的激活以及碳代谢基因转录本的变化 (例如，磷酸烯醇丙酮酸羧激酶，肉碱棕榈酰转移酶1，肝葡萄糖激酶和脂肪酸合成酶)。早期还观察到餐后血糖浓度降低; 我们推测这些归因于对胰岛素的敏感性增强和葡萄糖利用率增加，AMPK诱导葡萄糖转运蛋白GLUT4转运至细胞膜的可能作用以及己糖激酶表达增加。其他迟发性变化 (第4周) 包括乳酸和游离脂肪酸的血清浓度增加，肝糖原和甘油三酸酯和总胆固醇的血清浓度降低。鉴定生物素缺乏的早期特定分子和代谢紊乱可能有助于鉴定这种维生素的边缘缺乏的个体，这在正常人的怀孕中很常见。对其他维生素缺乏症 (例如这一种) 的时间过程的研究可能有助于更好地理解和应对其影响。

BACKGROUND & AIMS: BACKGROUND:Anemia and vitamin D deficiency are two important public health issues that may accompany many acute and chronic diseases. Several studies conducted in recent years have suggested that vitamin D deficiency is associated with anemia in healthy and patient populations. The aim of the study is to investigate the relationship between vitamin D deficiency and anemia. METHODS:The data of 9,590 adults aged 18 - 64, who applied for periodic medical examination to family medicine polyclinics of a training hospital between 2016 and 2018, were evaluated retrospectively. Individuals were classified into three groups as iron deficiency, iron deficiency anemia, and anemia; and 25 hydroxy vitamin D (25(OH)D) levels were classified into three groups as deficiency, insufficiency, and sufficiency. The groups were compared with respect to study parameters. RESULTS:Of the participants, 2,395 were male (25.0%) (mean age = 43.75 ± 13.43) and 7,195 (75.0%) were female (mean age = 42.93 ± 12.85). The number of anemic patients was 1,470 (15.3%) while the number of patients having no symptoms of anemia was 8,120 (84.7%). Serum hemoglobin (Hgb), iron, and ferritin levels were found to be significantly lower in the group with 25(OH)D deficiency than in the group of those with no deficiency. The mean 25(OH)D levels were observed to be significantly lower in those having anemia (17.4 ng/mL) than in those who do not (20.2 ng/mL), in those having iron deficiency (18.2 ng/mL) than in those who do not (20.5 ng/mL), and in those having iron deficiency anemia (16.6 ng/mL) than in those who do not (20.1 ng/mL) (all p-values are < 0.001). CONCLUSIONS:The findings of this large study population, who live in a Mediterranean city which is sunny for 300 days of the year, indicate that 25(OH)D deficiency is significantly associated with iron deficiency and/or anemia.

背景与目标：

BACKGROUND & AIMS: :Vitamin D deficiency is a common finding in individuals with cystic fibrosis (CF), despite routine supplementation. Hypovitaminosis D is often the result of fat malabsorption, but other contributors include increased latitude, poor nutritional intake, decreased sun exposure, impaired hydroxylation of vitamin D, and non-adherence to the prescribed vitamin D regimen. Vitamin D is critical for calcium homeostasis and optimal skeletal health, and vitamin D deficiency in CF can lead to skeletal complications of osteopenia and osteoporosis. Over time, our understanding of treatment regimens for vitamin D deficiency in CF has evolved, leading to recommendations for higher doses of vitamin D to achieve target levels of circulating 25-hydroxyvitamin D. There is also some evidence that vitamin D deficiency may have non-skeletal consequences such as an increase in pulmonary exacerbations. The exact mechanisms involved in the non-skeletal complications of vitamin D deficiency are not clearly understood, but may involve the innate immune system. Future clinical studies are needed to help address whether vitamin D has a role in CF beyond skeletal health.

背景与目标： : 尽管常规补充，维生素d缺乏症是囊性纤维化 (CF) 患者的常见发现。维生素d缺乏通常是脂肪吸收不良的结果，但其他因素包括纬度增加，营养摄入差，日晒减少，维生素d的羟基化受损以及不遵守规定的维生素d方案。维生素d对于钙稳态和最佳骨骼健康至关重要，CF中的维生素d缺乏会导致骨质减少和骨质疏松症的骨骼并发症。随着时间的推移，我们对CF中维生素d缺乏症的治疗方案的理解不断发展，导致建议使用更高剂量的维生素d来达到循环25-羟基维生素d的目标水平。还有一些证据表明，维生素d缺乏可能会导致非骨骼后果，例如肺加重的增加。维生素d缺乏的非骨骼并发症的确切机制尚不清楚，但可能涉及先天免疫系统。未来的临床研究需要帮助解决维生素d是否在骨骼健康之外的CF中发挥作用。

BACKGROUND & AIMS: :Our graphical review expands the analysis of cancer vulnerabilities for high dose vitamin C, based on several facts, illustrating the cytotoxic potential of the ascorbate free radical (AFR) via impairment of mitochondrial respiration and the mechanisms of its elimination in mammals by the membrane-bound NADH:cytochrome b5 oxidoreductase 3 (Cyb5R3). We propose that vitamin C can function in "protective mode" or "destructive mode" affecting cellular homeostasis, depending on the intracellular "steady-state" concentration of AFR and differential expression/activity of Cyb5R3 in cancerous and normal cells. Thus, a specific anti-cancer effect can be achieved at high doses of vitamin C therapy. The review is intended for a wide audience of readers - from students to specialists in the field.

背景与目标： : 我们的图形综述基于几个事实，扩展了对高剂量维生素c的癌症脆弱性的分析，说明了抗坏血酸自由基 (AFR) 通过线粒体呼吸受损的细胞毒性潜力及其通过膜结合的NADH在哺乳动物中消除的机制: 细胞色素b5氧化还原酶3 (Cyb5R3)。我们建议维生素c可以以 “保护模式” 或 “破坏模式” 起作用，从而影响细胞稳态，这取决于AFR的细胞内 “稳态” 浓度以及癌细胞和正常细胞中Cyb5R3的差异表达/活性。因此，高剂量的维生素c治疗可以达到特定的抗癌效果。该评论面向广大读者-从学生到该领域的专家。

BACKGROUND & AIMS: :Vitamin D is suggested to have a role in the coupling of bone resorption and formation. Compared with women, men are believed to have more stable bone remodeling, and thus, are considered less susceptible to the seasonal variation of calcitropic hormones. We examined whether seasonal variation exists in calcitropic hormones, bone remodeling markers, and BMD in healthy men. Furthermore, we determined which vitamin D intake is required to prevent this variation. Subjects (N = 48) were healthy white men 21-49 yr of age from the Helsinki area with a mean habitual dietary intake of vitamin D of 6.6 +/- 5.1 (SD) microg/d. This was a 6-mo double-blinded vitamin D intervention study, in which subjects were allocated to three groups of 20 microg (800 IU), 10 microg (400 IU), or placebo. Fasting blood samplings were collected six times for analyses of serum (S-)25(OH)D, iPTH, bone-specific alkaline phosphatase (BALP), and TRACP. Radial volumetric BMD (vBMD) was measured at the beginning and end of the study with pQCT. Wintertime variation was noted in S-25(OH)D, S-PTH, and S-TRACP (p < 0.001, p = 0.012, and p < 0.05, respectively) but not in S-BALP or vBMD in the placebo group. Supplementation inhibited the winter elevation of PTH (p = 0.035), decreased the S-BALP concentration (p < 0.05), but benefited cortical BMD (p = 0.09) only slightly. Healthy men are exposed to wintertime decrease in vitamin D status that impacts PTH concentration. Vitamin D supplementation improved vitamin D status and inhibited the winter elevation of PTH and also decreased BALP concentration. The ratio of TRACP to BALP shows the coupling of bone remodeling in a robust way. A stable ratio was observed among those retaining a stable PTH throughout the study. A daily intake of vitamin D in the range of 17.5-20 microg (700-800 IU) seems to be required to prevent winter seasonal increases in PTH and maintain stable bone turnover in young, healthy white men.

背景与目标： : 建议维生素d在骨吸收和形成的耦合中起作用。与女性相比，男性被认为具有更稳定的骨骼重塑，因此被认为不太容易受到钙调激素的季节性变化的影响。我们检查了健康男性的钙蛋白激素，骨重塑标志物和BMD是否存在季节性变化。此外，我们确定了需要摄入哪种维生素d来防止这种变化。受试者 (N = 48) 是来自赫尔辛基地区的21-49岁健康白人，平均习惯性饮食摄入的维生素d为6.6/- 5.1 (SD) microg/D。这是一项6个月的双盲维生素d干预研究，其中将受试者分配到三组20微克 (800 IU)，10微克 (400 IU) 或安慰剂。空腹采血六次，以分析血清 (S-)25(OH)D，iPTH，骨特异性碱性磷酸酶 (BALP)，和TRACP。在研究开始和结束时用pQCT测量径向体积BMD (vBMD)。在S-25(OH)D、S-PTH和S-TRACP中观察到冬季变化 (p <0.001，p = 0.012和p <0.05，但在安慰剂组的S-BALP或vBMD中没有。补充抑制冬季PTH升高 (p = 0.035)，降低S-BALP浓度 (p <0.05)，但对皮质骨密度 (p = 0.09) 仅略有益处。健康男性暴露于影响PTH浓度的维生素d状态的冬季降低。补充维生素d改善了维生素d状态，抑制了PTH的冬季升高，也降低了BALP浓度。TRACP与BALP的比率显示了骨重塑的耦合以一种稳健的方式。在整个研究中，在保持稳定的PTH的人群中观察到稳定的比例。每天摄入17.5-20微克 (700-800 IU) 的维生素d似乎需要防止冬季PTH季节性增加，并保持年轻时的稳定骨转换，健康的白人。

BACKGROUND & AIMS: :Background: There have been various articles reporting relationship between Vitamin D (VitD) and celiac disease (CeD), but results remain controversial. This study aimed to conduct a meta-analysis to systematically review and quantify the relationship between VitD and CeD. Moreover, difference in Vitamin D Receptor (VDR) genotypes between CeD patients and controls was also analyzed.Methods: Articles published until July 20, 2019 in the PubMed, MEDLINE, and EMBASE databases were searched. According to the inclusion and exclusion criteria, relevant statistical data were collated and extracted, which were finally analyzed by STATA15.1.Results: 27 articles and 28 sets of data were included. It showed that average 25(OH)D level in CeD patients was 8.36 nmol/L lower than controls (Weighted Mean Difference (WMD) = -8.36, 95% CI = [-14.63, -2.09] nmol/L). After gluten-free diet treatment, we found that average 25(OH)D level in treated patients was 15.6 nmol/L higher than untreated patients (WMD = 15.6, 95% CI = [5.96, 25.23] nmol/L). In addition, 25(OH)D level in treated patients was close to healthy controls (WMD = -2.82, 95% CI = [-6.45, 0.73] nmol/L). However, genetic polymorphism analysis showed that there is no difference in VDR genotypes between CeD and control.Conclusions: CeD had decreased serum 25(OH)D levels, which returned to normal after treatment, suggesting that VitD may play a role in the development of CeD. The directionality of this association cannot be confirmed from cross-sectional studies. Demonstration of a causal role of VitD deficiency in CeD development in future studies could have important therapeutic implications.

背景与目标： 背景: 有许多文章报道了维生素d (VitD) 与乳糜泻 (CeD) 之间的关系，但结果仍存在争议。本研究旨在进行荟萃分析，以系统地回顾和量化VitD与CeD之间的关系。此外，还分析了CeD患者和对照组之间维生素d受体 (VDR) 基因型的差异。方法: 搜索PubMed，MEDLINE和EMBASE数据库中直到2019年7月20日发表的文章。根据纳入和排除标准，整理并提取相关统计数据，最后通过stata15.1进行分析。结果: 纳入27篇文章，28组数据。结果表明，CeD患者的平均25(OH)D水平比对照组低8.36  nmol/L (加权平均差 (WMD) = -8.36，95% CI = [-14.63，-2.09] nmol/L)。我们发现接受治疗的患者的平均25(OH)D水平比未接受治疗的患者高15.6  nmol/L (WMD = 15.6，95% CI = [5.96，25.23] nmol/L)。25(OH)D水平接近健康对照组 (WMD = -2.82，95% CI = [-6.45，0.73] nmol/L)。然而，遗传多态性分析表明，CeD和对照组之间的VDR基因型没有差异。结论: ceD降低了血清25(OH)D水平，治疗后恢复正常，提示VitD可能在CeD的发展中起作用。这种关联的方向性不能从横断面研究中得到证实。在未来的研究中，证明VitD缺乏症在CeD发展中的因果作用可能具有重要的治疗意义。